Various complexes of monodentate and bidentate ligands with technetium having been made and studied. These complexes generally were made for use in studies to determine the various oxidation states of technetium and for other research regarding the structure of such complexes and metal-coordination chemistry. Such studies have been reported in, for instance, Chemistry and Industry, pp. 347-8 (Mar. 26, 1960); J. Inorg. Nucl. Chem., Vol. 28, pp. 2293-96 (1966); Aust. J. Chem., 23, pp. 453-61 (1970); Inorganic Chem., Vol. 16, No. 5, pp. 1041-48 (1977); J. Inorg. Nucl. Chem., Vol. 39, pp. 1090-92 (1977); and J. C. S. Dalton, pp. 125-30 (1976).
In a presentation to the American Pharmaceutical Association, E. A. Deutsch disclosed that certain complexes of DIARS, i.e. ##STR1## and Tc-99m, and certain complexes of DMPE, i.e. (CH.sub.3).sub.2 PCH.sub.2 CH.sub.2 P(CH.sub.3).sub.2 and Tc-99m, may be useful as radio-diagnostic agents for myocardial and hepatobiliary imaging. (.sup.99m Tc-(DMPE).sub.2 Cl.sub.2)+ and [.sup.99m Tc-(DIARS).sub.2 Br.sub.2 ]+ were prepared by Deutsch by heating in an open flask a reaction mixture containing the appropriate hydrogen halide in aqueous alcohol solution, .sup.99m Tc-sodium pertechnetate, and ortho-phenylenebis(dimethylarsine), i.e. DIARS, orbis-(1,2-dimethylphosphino)ethane, i.e. DMPE. The reaction was reported to take about 30 minutes. The labelled complex was then purified by chromatographic methods involving ion exchange columns.
The labelled complex produced according to the procedure of Deutsch has several practical disadvantages. The procedure requires handling several ingredients including an organic solvent to make the reaction mixture and then purifying the resulting radiolabelled complex by chromatography. Each of these handling steps can contaminate the system and final product. The purification step further requires additional time for preparation of the final product. These steps require a skilled technician and are performed at the site of use, just prior to use. Thus, a complex, time consuming chemical preparation is required during which sterility of ingredients and containers is difficult to maintain. Thus, to assure freedom from contamination, a final sterilization step is required, which further adds to preparation time. Because Tc-99m has a short half-life, lengthy preparation methods are undesirable. Thus, the complexity of the preparation, both with regard to maintaining sterile conditions and to purification of the .sup.99m Tc-labelled complex make the Deutsch procedure undesirable.
Certain commercially available hepatobiliary imaging agents, such as .sup.99m Tc-labelled disofenin, take up to thirty (30) minutes to obtain an image of the hepatobiliary transit. It is desirable to have hepatobility agents with faster blood clearance rates that would enable the visualization of the hepatobiliary transit in less time.